Michael Yafi

Deletion of G-protein-coupled receptor 55 promotes obesity by reducing physical activity

Background/Objectives:Cannabinoid receptor 1 (CB1) is the best-characterized cannabinoid receptor, and CB1 antagonists are used in clinical trials to treat obesity. Because of the wide range of CB1 functions, the side effects of CB1 antagonists pose serious concerns. G-protein-coupled receptor 55 (GPR55) is an atypical cannabinoid receptor, and its pharmacology and functions are distinct from CB1. GPR55 regulates neuropathic pain, gut, bone, immune functions and motor coordination. GPR55 is expressed in various brain regions and peripheral tissues. However, the roles of GPR55 in energy and glucose homeostasis are unknown. Here we have investigated the roles of GPR55 in energy balance and insulin sensitivity using GPR55-null mice (GPR55−/−).Methods:Body composition of the mice was measured by EchoMRI. Food intake, feeding behavior, energy expenditure and physical activity of GPR55−/− mice were determined by indirect calorimetry. Muscle function was assessed by forced treadmill running test. Insulin sensitivity was evaluated by glucose and insulin tolerance tests. Adipose inflammation was assessed by flow cytometry analysis of adipose tissue macrophages. The expression of inflammatory markers in adipose tissues and orexigenic/anorexigenic peptides in the hypothalamus was also analyzed by real-time PCR.Results:GPR55−/− mice had normal total energy intake and feeding pattern (i.e., no changes in meal size, meal number or feeding frequency). Intriguingly, whereas adult GPR55−/− mice only showed a modest increase in overall body weight, they exhibited significantly increased fat mass and insulin resistance. The spontaneous locomotor activity of GPR55−/− mice was dramatically decreased, whereas resting metabolic rate and non-shivering thermogenesis were unchanged. Moreover, GPR55−/− mice exhibited significantly decreased voluntary physical activity, showing reduced running distance on the running wheels, whereas muscle function appeared to be normal.Conclusions:GPR55 has an important role in energy homeostasis. GPR55 ablation increases adiposity and insulin resistance by selectively decreasing physical activity, but not by altering feeding behavior as CB1.

Health-related quality of life and cognitive functioning in pediatric short stature: Comparison of growth-hormone-naïve, growth-hormone-treated, and healthy samples

The objective of this study was to evaluate the impact of short stature on generic health-related quality of life (HRQOL) and cognitive functioning in pediatric patients. Eighty-nine youth, 48 who were initially seen with short stature (SS group) and 41 with a history of short stature being treated with growth hormone (GHT group) and one of their legal guardians participated in the study. HRQOL and cognitive functioning were assessed using the PedsQL™ 4.0 Generic Core Scales and PedsQL™ Cognitive Functioning Scale. Comparisons were made between the study groups and with a previously obtained matched healthy sample. For the GHT group, height Z score was found to be a positive predictor of overall HRQOL while duration of GHT was found to be a predictor of physical functioning. For the SS group, the difference between midparental height Z score and height Z score was found to be a negative predictor of overall HRQOL and cognitive functioning. Comparison with the healthy sample demonstrated significant negative impact on HRQOL for child self-report and on HRQOL and cognitive functioning for parent proxy-report in both study groups. The GHT group had a significantly higher child self-reported Physical Functioning score than the SS group (effect size (ES) = 0.52, p < 0.05). In conclusion, the GHT group had slightly better HRQOL scores than the SS group, but the difference was not statistically significant. Both groups had significantly lower HRQOL and cognitive functioning scores than healthy sample. Predictors of HRQOL and cognitive functioning found in this study lend support to the use of the PedsQL™ 4.0 Generic Score Scales and PedsQL™ Cognitive Functioning Scale in routine assessment of children with short stature in order to identify children at increased risk for impaired HRQOL and cognitive functioning.

Sexual precocity in a 2-year-old boy caused by indirect exposure to testosterone cream

OBJECTIVE To report a rare case of sexual precocity caused by inadvertent exposure to testosterone cream. METHODS We report the clinical, laboratory, and radiologic findings of a boy presenting with sexual precocity; review short- and long-term consequences; and discuss preventative measures. RESULTS A 2 and 7/12-year-old boy had onset of pubic hair without testicular enlargement and a period of rapid linear growth. History revealed possible topical testosterone exposure from close contact with the childs father. On physical examination, the boy had Tanner stage II pubic hair distribution. Laboratory evaluation findings were normal for age except for the testosterone concentration, which was comparable to late-pubertal and adult male levels at 371 ng/dL (reference range, <3-10 ng/dL for prepubertal male). Brain magnetic resonance imaging and testicular ultrasonography were normal. Skeletal age was advanced at age 4 and 6/12 years. Repeated laboratory evaluation, after the childs father ceased testosterone use, revealed a normal testosterone concentration of 10 ng/dL. Thus, this boys sexual precocity was attributed to inadvertent exogenous androgen exposure. CONCLUSIONS When examining a child with sexual precocity, asking about possible exposure to androgens and estrogens is important. Patients being treated with these products should be educated about the possible risks of testosterone exposure to others and ways to limit exposure.

Expanded newborn screening in Texas: A survey and educational module addressing the knowledge of pediatric residents

Purpose: To assess the effectiveness of an educational module as a tool for improving the knowledge of pediatric residents about newborn screening and its expansion in Texas.Methods: The study population consisted of 63 pediatric residents from the University of Texas at Houston, Baylor College of Medicine in Houston, and the University of Texas Medical Branch in Galveston. Residents were invited to participate in the study during daily scheduled didactic lectures in their respective residency programs. Questionnaires were distributed to the residents both before and after the presentation of an educational module about newborn screening in Texas to assess whether knowledge was gained from the presentation.Results: Analysis of questionnaires from the full group of participants showed a substantial increase in knowledge about newborn screening in Texas after the presentation of the educational module. This included a 45.4% increase in knowledge about pre-expansion newborn screening conditions and a 308.4% increase in knowledge about expanded newborn screening conditions (P ≤ 0.001).Conclusions: Our results suggest that an educational module about newborn screening like the one we created for this study would be an effective tool for improving the knowledge of pediatric residents on a larger scale.

And the best treatment for diabetes poor compliance is

272 PRACTICAL DIABETES VOL. 33 NO. 8 COPYRIGHT

Two cases of type 1 diabetes in adolescents: to test blood glucose or not to test?

Coping with diabetes and managing daily challenges remain a major factor in adolescents. After initial diagnosis, the daily management of diabetes happens at home. Dealing with diabetes on a daily basis affects dietary habits and physical activities. Daily multiple testing of finger blood glucose levels increases the emotional burden of the disease. Clarifying the responsibility for diabetes self‐management should be a continuous dialogue between adolescents and parents.